Five people were believed to be missing hours after the blasts on Tuesday and flames ravaged the Silver Lake Nursing Home in Bristol Township, about 30km northeast of Philadelphia, Bristol Township Fire Marshal Kevin Dippolito said.
Besides the two people killed, an unspecified number of survivors were injured, Dippolito said, adding that numerous patients and staff initially trapped inside a demolished portion of the building were rescued.
The Bucks County emergency dispatch centre received first reports of an explosion shortly after 2pm.
Dippolito said the first firefighters arriving on the scene, some from a fire-and-rescue station across the street, encountered "a major structural collapse," with part of the building's first floor crumbling into the basement below.
He said numerous victims were extricated from debris, blocked stairwells and stuck elevators, while firefighters ventured into the collapsed basement zone and pulled at least two more people to safety before retreating amid lingering gas fumes.
"We got everyone out that we could, that we could find, that we could see, and we exited the building," Dippolito said.
"Within approximately 15 to 30 seconds of us exiting the building, knowing there was a heavy odor of natural gas around us, there was another explosion and fire."
The front of the structure appeared to have been blasted away from the inside, but the majority of the facility remained standing, though most of its windows were shattered, according to a Reuters photographer on the scene.
News footage from WPVI-TV, an ABC News affiliate, showed roaring flames and smoke billowing from the crippled building shortly after the first explosion.
The precise number of patients and staff inside at the time was not immediately known. The nursing home is certified for up to 174 beds, according to an official Medicare provider site.
More than 50 patients, ranging in age from 50 to 95, are typically in the building at any one time, WCAU-TV reported, citing a nurse employed by the facility who arrived on the scene after the blast. About five hours later, nursing home officials had informed authorities that all patients had been accounted for, Dippolito said.
In the early moments following the initial explosion, bystanders rushed to assist police and firefighters in escorting people to safety, Bristol Township Police Lieutenant Sean Cosgrove told local media earlier.
"This is the Pennsylvania way, neighbours helping neighbours in a moment of need," Governor Josh Shapiro said at the news briefing with fire and police officials.
Five hours after the incident, Dippolito said fire and rescue personnel were still treating the search effort as a rescue operation as heavy equipment was brought in to help clear away larger pieces of rubble.
